Truncation of IGF-I yields two mitogens for retinal Müller glial cells

In the CNS only a truncated form of insulin-like growth factor-I (IGF-I) is detected. Although truncated IGF-I (t-IGF-I) retains mitogenicity, growth promoting activities have not been detected for the tripeptide that is cleaved from IGF-I during truncation. Here, we asked whether the tripeptide is itself a growth factor. Using cultured Müller glial cells from the adult human retina, we found that the cleaved tripeptide, glycine-proline-glutamate, stimulated the proliferation of these cells. Pharmacological experiments indicated that this proliferative effect involves activation of N-methyl-D-aspartate (NMDA) receptors. In addition, t-IGF-I was also mitogenic in our culture system and had an EC50 markedly less than that for IGF-I. Thus, truncation of IGF-I may be a mechanism to augment the mitogenic effect of this gene product by creating a more potent variant and a cleaved tripeptide that is itself a mitogen.